{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T02:02:17Z","timestamp":1781316137338,"version":"3.54.1"},"reference-count":38,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Indole-oxazole and indole-oxadiazole scaffolds, inspired by natural products, provide versatile platforms for the development of selective COX inhibitors. In this study, a novel series of indol-oxadiazole derivatives was rationally designed by incorporating N-alkyl-substituted indole moieties at the 5-position and optimizing aryl substitutions at the 2-position of the oxadiazole core. The synthesized compounds were systematically evaluated for COX-1 and COX-2 inhibition\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    , revealing potent and selective activity. The compounds exhibited potent\n                    <jats:italic>in\u00a0vitro<\/jats:italic>\n                    COX inhibition, with\n                    <jats:bold>IO-2<\/jats:bold>\n                    showing balanced dual activity against COX-1 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a00.198\u00a0\u00b1\u00a00.022\u202f\u00b5M) and COX-2 (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a00.158\u00a0\u00b1\u00a00.028\u202f\u00b5M), and\n                    <jats:bold>IO-13<\/jats:bold>\n                    displaying strong COX-1 inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a00.175\u00a0\u00b1\u00a00.063\u202f\u00b5M). Celecoxib served as the reference COX-2 inhibitor (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00a0=\u00a00.119\u00a0\u00b1\u00a00.055\u202f\u00b5M). Molecular docking and dynamics simulations provided insights into binding interactions and the stability of the COX complex within the COX active site. Selected derivatives were well tolerated in healthy cell lines, indicating favorable safety profiles. Structure-activity relationship analysis highlighted the critical role of the indole nucleus and strategic oxadiazole substitutions in modulating COX inhibitory potency and selectivity. These findings establish indole\u2013oxadiazoles as a promising scaffold for selective COX inhibition and a foundation for future rational drug design.\n                  <\/jats:p>","DOI":"10.1515\/znc-2026-0075","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:52:40Z","timestamp":1781311960000},"source":"Crossref","is-referenced-by-count":0,"title":["Rational design and biological evaluation of naturally inspired indole-oxadiazole derivatives as potent COX inhibitors"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-7177","authenticated-orcid":false,"given":"Burak","family":"Kuzu","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Van Yuzuncu Yil University , Van , 65080 , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0499-436X","authenticated-orcid":false,"given":"Derya","family":"Osmaniye","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Anadolu University , Eski\u015fehir , T\u00fcrkiye"},{"name":"Central Analysis Laboratory, Faculty of Pharmacy , Anadolu University , Eski\u015fehir , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00fc\u015fra","family":"Korkut-\u00c7elikate\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy , Anadolu University , Eski\u015fehir , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zafer As\u0131m","family":"Kaplanc\u0131kl\u0131","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy , Anadolu University , Eski\u015fehir , T\u00fcrkiye"},{"name":"Department of Pharmacy Services , Vocational School of Health Services, Bilecik Seyh Edebali University , Eski\u015fehir , T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"2026061301344870323_j_znc-2026-0075_ref_001","doi-asserted-by":"crossref","unstructured":"Rodrigues, T, Reker, D, Schneider, P, Schneider, G. 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